Rotavirus 2/6 virus-like particles administered intranasally in mice, withor without the mucosal adjuvants cholera toxin and Escherichia coli heat-labile toxin, induce a Th1/Th2-like immune response

We investigated the rotavirus-specific lymphocyte responses induced by intr anasal immunization of adult BALB/c mice with rotavirus 2/6 virus-like part icles (2/6-VLPs) of the bovine RF strain, by assessing the profile of cytok ines produced after in vitro restimulation and serum and fecal antibody res ponses. The cytokines produced by splenic cells were first evaluated. Intra nasal immunization with 50 mug of 2/6-VLPs induced a high serum antibody re sponse, including immunoglobulin G1 (IgG1) and IgG2a, a weak fecal antibody response, and a mixed Th1/Th2-like profile of cytokines characterized by g amma interferon and interleukin 10 (IL-10) production and very low levels o f IL-2, IL-4, and IL-5. Intranasal immunization with 10 mug of 2/6-VLPs coa dministered with the mucosal adjuvants cholera toxin and Escherichia coli h eat-labile toxin (LT) considerably enhanced the Th1/Th2-like response; nota bly, significant levels of IL-2, IL-4, and IL-5 were observed. Since rotavi rus is an enteric pathogen, we next investigated the production of IL-2 and IL-5, as being representative of Th1 and Th2 responses, by Peyer's patch a nd mesenteric lymph node cells from mice immunized intranasally with 2/6-VL Ps and LT. The results were compared to those obtained from splenic and cer vical lymph node cells. We found that both cytokines were produced by cells from each of these lymphoid tissues. These results confirm the Th1/Th2-lik e response observed at the systemic level and show, on the assumption that T cells are the primary cells producing the cytokines after in vitro restim ulation, that rotavirus-specific T lymphocytes are present in the intestine after intranasal immunization with 2/6-VLPs and LT.